TY - JOUR T1 - Insufficient beta-lactam concentrations in the early phase of severe sepsis and septic shock89 JF - Crit Care Y1 - 2010 A1 - Taccone,F.S. A1 - Laterre,P.F. A1 - Dugernier,T. A1 - Spapen,H. A1 - I. Delattre A1 - Wittebole,X. A1 - D. de Backer A1 - Layeux,B. A1 - P.E. Wallemacq A1 - Vincent,J.L. A1 - Jacobs,F. KW - 0 KW - a KW - acid KW - administration & dosage KW - Agent KW - Agents KW - ALL KW - analogs & derivatives KW - Anti-Bacterial Agents KW - Antibiotic KW - antibiotics KW - Antimicrobial KW - article KW - Belgian KW - Belgium KW - beta-Lactams KW - blood KW - Bruxelles KW - care KW - Ceftazidime KW - cephalosporin KW - Cephalosporins KW - chromatography KW - Chromatography,High Pressure Liquid KW - Clinical KW - de KW - Diagnosis KW - DRUG KW - drug therapy KW - Drug Therapy,Combination KW - drugs KW - electronic KW - European KW - Female KW - hospital KW - HPLC KW - Humans KW - im KW - intensive care KW - intensive care unit KW - intensive care units KW - interval KW - IS KW - journal KW - Less KW - liquid chromatography KW - Male KW - metabolism KW - method KW - methods KW - Microbial Sensitivity Tests KW - middle aged KW - n KW - ON KW - pathogen KW - Patient KW - patients KW - Penicillanic Acid KW - period KW - Pharmacokinetic KW - pharmacokinetics KW - Piperacillin KW - profile KW - Prospective Studies KW - Pseudomonas KW - Pseudomonas aeruginosa KW - Research KW - Research Support KW - result KW - results KW - SB - IM KW - Sepsis KW - serum KW - Shock,Septic KW - STANDARD KW - study KW - Target KW - TESTING KW - therapeutic use KW - Thienamycins KW - time KW - Times KW - treatment KW - WHO AB - INTRODUCTION: Altered pharmacokinetics (PK) in critically ill patients can result in insufficient serum beta-lactam concentrations when standard dosages are administered. Previous studies on beta-lactam PK have generally excluded the most severely ill patients, or were conducted during the steady-state period of treatment. The aim of our study was to determine whether the first dose of piperacillin-tazobactam, ceftazidime, cefepime, and meropenem would result in adequate serum drug concentrations in patients with severe sepsis and septic shock. METHODS: Open, prospective, multicenter study in four Belgian intensive care units. All consecutive patients with a diagnosis of severe sepsis or septic shock, in whom treatment with the study drugs was indicated, were included. Serum concentrations of the antibiotics were determined by high-pressure liquid chromatography (HPLC) before and 1, 1.5, 4.5 and 6 or 8 hours after administration. RESULTS: 80 patients were treated with piperacillin-tazobactam (n = 27), ceftazidime (n = 18), cefepime (n = 19) or meropenem (n = 16). Serum concentrations remained above 4 times the minimal inhibitory concentration (T > 4 x MIC), corresponding to the clinical breakpoint for Pseudomonas aeruginosa defined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST), for 57% of the dosage interval for meropenem (target MIC = 8 mug/mL), 45% for ceftazidime (MIC = 32 mug/mL), 34% for cefepime (MIC = 32 mug/mL), and 33% for piperacillin-tazobactam (MIC = 64 mug/mL). The number of patients who attained the target PK profile was 12/16 for meropenem (75%), 5/18 for ceftazidime (28%), 3/19 (16%) for cefepime, and 12/27 (44%) for piperacillin-tazobactam. CONCLUSIONS: Serum concentrations of the antibiotic after the first dose were acceptable only for meropenem. Standard dosage regimens for piperacillin-tazobactam, ceftazidime and cefepime may, therefore, be insufficient to empirically cover less susceptible pathogens in the early phase of severe sepsis and septic shock VL - 14 CP - 4 U1 - 38883 M3 - cc9091 [pii];10.1186/cc9091 [doi] ER -